The invention relates to antibacterial amide macrocycles and methods for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for manufacturing medicaments for the treatment and/or prophylaxis of diseases, in particular of bacterial infections.
WO 03/106480 and WO 04/012816 describe macrocycles of the biphenomycin B type which have antibacterial activity and have amide and ester substituents respectively.
U.S. Pat. No. 3,452,136, thesis of R. U. Meyer, Stuttgart University, Germany (1991), thesis of V. Leitenberger, Stuttgart University, Germany (1991), Synthesis (1992) (10):1025-1030, J. Chem. Soc., Perkin Trans. 1 (1992) (1):123-130, J. Chem. Soc., Chem. Commun. (1991) (10):744, Synthesis (1991) (5):409-413, J. Chem. Soc., Chem. Commun. (1991) (5):275-277, J. Antibiot. (1985) 38(11):1462-1468, J. Antibiot. (1985) 38(11):1453-1461 describe the natural product biphenomycin B as having antibacterial activity. Some steps in the synthesis of biphenomycin B are described in Synlett (2003), 4, 522-526.
Chirality (1995) 7(4):181-1892, J. Antibiot. (1991) 44(6):674-677, J. Am. Chem. Soc. (1989) 111(19):7323-7327, J. Am. Chem. Soc. (1989) 111(19):7328-7333, J. Org. Chem. (1987) 52(24):5435-5437, Anal. Biochem. (1987) 165(1):108-113, J. Org. Chem. (1985) 50(8):1341-1342, J. Antibiot. (1993) 46(3):C-2, J. Antibiot. (1993) 46(1):135-140, Synthesis (1992) (12):1248-1254, Appl. Environ. Microbiol. (1992) 58(12):3879-3888, J. Chem. Soc., Chem. Commun. (1992) (13):951-953 describe a structurally related natural product, biphenomycin A, which has a further substitution with a hydroxy group on the macrocycle.
The natural products in terms of their properties do not comply with the requirements for antibacterial medicaments. Although structurally different agents with antibacterial activity are available on the market, the development of resistance is a regular possibility. Novel agents for good and more effective therapy are therefore desirable.